Dobutamine Stress Echocardiography for Management of Low-Flow, Low-Gradient Aortic Stenosis

Background: In the American College of Cardiology/American Heart Association guidelines, patients are considered to have true-severe stenosis when the mean gradient (MG) is ≥40 mm Hg with an aortic valve area (AVA) ≤1 cm² during dobutamine stress echocardiography (DSE). However, these criteria have not been previously validated. Objectives: The aim of this study was to assess the value of these criteria to predict the presence of true-severe AS and the occurrence of death in patients with low-flow, low-gradient aortic stenosis (LF-LG AS). Methods: One hundred eighty-six patients with low left ventricular ejection fraction (LVEF) LF-LG AS were prospectively recruited and underwent DSE, with measurement of the MG, AVA, and the projected AVA (AVA_Proj), which is an estimate of the AVA at a standardized normal flow rate. Severity of AS was independently corroborated by macroscopic evaluation of the valve at the time of valve replacement in 54 patients, by measurement of the aortic valve calcium by computed tomography in 25 patients, and by both methods in 8 patients. According to these assessments, 50 of 87 (57%) patients in the study cohort had true-severe stenosis. Results: Peak stress MG ≥40 mm Hg, peak stress AVA ≤1 cm², and the combination of peak stress MG ≥40 mm Hg and peak stress AVA ≤1 cm² correctly classified AS severity in 48%, 60%, and 47% of patients, respectively, whereas AVA_Proj ≤1 cm² was better than all the previous markers (p < 0.007), with 70% correct classification. Among the subset of 88 patients managed conservatively (47% of the cohort), 52 died during a follow-up of 2.8 ± 2.5 years. After adjustment for age, sex, functional capacity, chronic kidney failure, and peak stress LVEF, peak stress MG and AVA were not predictors of mortality in this subset. In contrast, AVA_Proj ≤1 cm² was a strong predictor of mortality under medical management (hazard ratio: 3.65; p = 0.0003). Conclusions: In patients with low LVEF LF-LG AS, the DSE criteria of a peak stress MG ≥40 mm Hg, or the composite of a peak stress MG ≥40 mm Hg and a peak stress AVA ≤1 cm² proposed in the guidelines to identify true-severe AS and recommend valve replacement, have limited value to predict actual stenosis severity and outcomes. In contrast, AVA_Proj better distinguishes true-severe AS from pseudo-severe AS and is strongly associated with mortality in patients under conservative management. (Multicenter Prospective Study of Low-Flow Low-Gradient Aortic Stenosis [TOPAS]; NCT01835028)